Wu T L, Vasavada R C, Yang K, Massfelder T, Ganz M, Abbas S K, Care A D, Stewart A F
Division of Endocrinology, Connecticut Veterans Affairs Medical Center, West Haven, Connecticut 06516, USA.
J Biol Chem. 1996 Oct 4;271(40):24371-81. doi: 10.1074/jbc.271.40.24371.
Parathyroid hormone-related protein (PTHrP) is initially translated as a preprohormone which is posttranslationally processed to yield a family of mature secretory forms. Most attention has focused on the amino-terminal portion of the molecule which is homologous to parathyroid hormone. It is clear, however, that a mid-region species of PTHrP is posttranslationally cleaved from the highly conserved mid-region of PTHrP, and that the amino terminus of this peptide is Ala38. The purposes of the current study were three: 1) to confirm that Arg37 immediately preceding Ala38 serves as a posttranslational processing site in the PTHrP precursor, 2) to determine the carboxyl terminus of the mid-region secretory species of PTHrP, and 3) to synthesize this authentic mid-region secretory form of PTHrP and determine whether it is biologically active. The results indicate that: 1) Arg37 is indeed a processing site in the PTHrP precursor; 2) three distinct mid-region PTHrP species are generated by posttranslational processing, PTHrP(38-94)amide, PTHrP(38-95), and most likely, PTHrP(38-101); and 3) synthetic mid-region PTHrP(38-94)amide is active in four different biological systems. These studies confirm the finding that PTHrP is a prohormone. More importantly, they define a novel, biologically active highly conserved mid-region secretory form of PTHrP.
甲状旁腺激素相关蛋白（PTHrP）最初被翻译为前激素原，经翻译后加工产生一系列成熟的分泌形式。大多数关注集中在该分子与甲状旁腺激素同源的氨基末端部分。然而，很明显，PTHrP的一种中间区域产物是从PTHrP高度保守的中间区域经翻译后切割产生的，且该肽的氨基末端是Ala38。本研究的目的有三个：1）确认紧接Ala38之前的Arg37作为PTHrP前体的翻译后加工位点；2）确定PTHrP中间区域分泌产物的羧基末端；3）合成这种真正的PTHrP中间区域分泌形式并确定其是否具有生物活性。结果表明：1）Arg37确实是PTHrP前体中的一个加工位点；2）翻译后加工产生三种不同的中间区域PTHrP产物，即PTHrP(38 - 94)酰胺、PTHrP(38 - 95)，很可能还有PTHrP(38 - 101)；3）合成的中间区域PTHrP(38 - 94)酰胺在四种不同的生物系统中具有活性。这些研究证实了PTHrP是一种激素原这一发现。更重要的是，它们定义了一种新型的、具有生物活性的高度保守的PTHrP中间区域分泌形式。
